The invention relates to a polymer, and more specifically to a bio-compatible and bio-degradable block copolymer and a nano particle comprising the same.
To improve curative effects and reduce side effects, an optimal drug delivery carrier which can precisely target at tumor cell and produce high drug concentration around the focus is required. Such carrier materials must be bio-compatible, bio-degradable, and be invisible to immune system detection to avoid macrophage attack. Common carrier materials comprise block copolymers. Some, however, lack bio-degradability, long-term stability, and invisibility to the immune cells in blood circulation.
Sugiyama provides a zwitterionic copolymer comprising a hydrophilic chain of 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) and a hydrophobic chain ends of cholesteryl with critical micelle concentration (CMC) of 2.5×10−4−2.7×10−5 wt % recited in Journal of Polymer Science Part A: Polymer Chemistry (2003) 1992-2000. Such material forms a complex with cholesterol molecules in condensed layer morphology with a 3.52 nm interval therebetween. This copolymer provides hemo-compatibility and encapsulates water-insoluble drugs by hydrophobic cholesterol groups attached on the polymer chains. The material, however, lacks bio-degradability.
Stenzel provides a zwitterionic block copolymer comprising poly(2-acryloyloxyethyl phosphorylcholine) and poly(butyl acrylate) with bio-compatibility formed by reversible addition fragmentation transfer (RAFT) recited in Macromolecular Bioscience (2004) 445-453. The nano particle formed in water and methanol binary solvent thereby has a diameter of about 100-180 nm. This copolymer, however, also lacks bio-degradability.
Nakabayashi provides a bio-degradable poly(L-lactic acid) (PLLA) material comprising phosphorylcholine such as L-α-glycerophosphorylcholine (LGPC) recited in Journal of Biomedical Materials Research part A (2003) 164-169. Various molecular weight PLLA materials can be polymerized using LGPC as an initiator. According to a blood cell experiment, as the phosphorylcholine content of PLLA increases, blood-cell adsorption reduces. This material, however, lacks micelle characteristics.
Oishi provides a novel zwitterionic poly(fumaramate) material comprising phosphorylcholine with CMC of about 1.7×10−3−1.0×10−3M recited in Polymer (1997) 3109-3115. The CMC is altered by conducting isopropyl and methyl groups to fumaramate. According to a bovine serum albumin adsorption experiment, as the phosphorylcholine content of poly(fumaramate) increases, bovine serum albumin adsorption is reduced.
Sommerdijk provides a polystyrene material comprising tetra(ethylene glycol) and phosphorylcholine bonded to its side chain with bio-compatibility recited in Journal of Polymer Science Part A: Polymer Chemistry (2001) 468-474. According protein adsorption experiment and in-vitro human dermal fibroblasts culture, only polystyrene material containing tetra(ethylene glycol) and phosphorylcholine can reduce protein adsorption and fibroblasts growth, as compared with polystyrene bonded with tetra(ethylene glycol) or phosphorylcholine alone.
Langer provides a bio-degradable injection-type nano particle comprising diblock (AB) or triblock (ABC) copolymer disclosed in U.S. Pat. Nos. 5,543,158 and 6,007,845. A is a hydrophilic chain such as poly(alkylene glycol), B is a hydrophobic chain such as PLGA, and C is a bio-active substance such as antibody. The particle can target at cells or organs by the bio-active substance bonded thereto. These applications, however, fail to disclose AB or ABC can provide invisibility to bio-recognition.
Kim provides a bio-degradable drug-contained micelle comprising diblock (BA) or triblock (ABA or BAB) copolymer with a preferable molecular weight of about 1430-6000 and a hydrophilic chain ratio of 50-70 wt % disclosed in U.S. Pat. No. 6,322,805. A is a bio-degradable hydrophobic chain and B is a hydrophilic chain such as PEG. Drugs such as paclitaxel are encapsulated by physical manner. The application, however, fails to disclose ABC-type triblock copolymer.
Marchant provides an anti-thrombosis triblock copolymer comprising a hydrophobic bio-degradable polymer and a hydrophilic polysaccharide chain such as dextran or heparin disclosed in U.S. Pat. No. 5,741,852.
Ishihara provides a method for preparing a phosphorylcholine-contained polymer in aqueous phase disclosed in U.S. Pat. No. 6,204,324. Polymerizable monomers, phosphorylcholine, are polymerized by adding initiator in aqueous medium. The results are then purified by a separation film, containing impurity less than 2000 ppm.